NICE has failed to recommend GSK’s Tyverb (lapatinib) or Roche’s Herceptin (trastuzumab) with aromatase inhibitors as a first line treatment for a particular type of breast cancer in final draft guidance.

The decision is based on uncertainties over the overall survival benefits compared to existing treatments of both medicines and the high cost of the treatments.

Sir Andrew Dillon, Chief Executive of NICE, said that while the two have been shown to reduce the growth and spread of breast cancer the extent of overall survival extension “appears to be small or difficult to quantify”.

Final guidance on the appraisal is now expected in June.

The guidance only advises the use of the drugs alongside aromatase inhibitors as a first line treatment option to delay the growth of advanced breast cancer that has spread and reacts with oestrogen or progesterone and has high levels of HER2.

Alongside the clinical benefits, NICE also raised concerns around the cost effectiveness of both products. GSK estimates that the most plausible incremental cost effectiveness ratio (ICER) for Tyverb is likely to be around £74,400 per QALY gained. Roche estimates the most plausible ICER for Herceptin to be around £51,000 per QALY gained – both far in excess of the £20,000-£30,000 NICE typically deems to be a cost effective use of NHS resources.

NICE has failed to recommend Roche’s Avastin (bevacizumab) for the first-line treatment of metastatic breast cancer after raising a number of uncertainties over its use in new draft guidance.

Its independent Appraisal Committee questioned the clinical benefit of the drug in overall survival and concluded its high cost was not a good use of NHS resources.

Sir Andrew Dillon, NICE Chief Executive, says the evidence provided “did not conclusively” demonstrate Avastin to be clinically and cost effective.

The breast cancer drug was being appraised when used in combination with the chemotherapy drug Xeloda (capecitabine).

Data provided by Roche had demonstrated that median progression-free survival benefit associated with Avastin plus Xeloda was 2.9 months greater than Xeloda monotherapy alone.

However, the Committee claimed it was unclear whether that benefit translated into an improvement in overall survival.

The Committee also raised the issue of a lack of data showing whether patients would have a better quality of life than if they were treated with chemotherapy alone.

Also, NICE noted that Roche’s cost-effectiveness figures were based on a specific subgroup of patients who had previously received a taxane, and not on the whole capecitabine cohort.

Given these uncertainties the Committee concluded it was not possible to arrive at a plausible Incremental Cost Effectiveness Ratio (ICER) per QALY gained for bevacizumab plus capecitabine compared with capecitabine alone for the whole patient population and were not able to recommend the treatment.

“We can’t recommend a drug that has not been shown to work as well as, or better than, current treatments and costs much more,” said Sir Andrew. “We want to ensure people have access to the best treatments the NHS can afford; bevacizumab has so far not been proven to be clinically or cost-effective.”

Breast cancer is one of the most common cancers in England. In the UK, it is estimated that more than 48,000 women and around 300 men are diagnosed with the disease each year.

The draft guidance is now open for consultation.

NICE has again failed to recommend the use of Eisai’s breast cancer drug Halaven (eribulin) after further questioning the treatment’s side-effects in new guidance.

Eisai had provided additional data after NICE’s original decision not to recommend the treatment back in November.

But NICE concluded the data, which analysed women previously treated with Xeloda (capecitabine), did not show “robust” survival advantage and decided there no “convincing cost effectiveness” for its use.

The Institute received one appeal on its earlier draft guidance. This was dismissed on all counts; however, the Appeal Panel did recommend that sections describing the adverse events experienced with the drug and its comparator were revised.

Halaven has been shown to potentially extend the life of women by 2.7 months compared with a ‘treatment of physician’s choice’. However, the cancer drug did not fulfil all of NICE’s end-of-life criteria.

Sir Andrew Dillon commented: “Although the evidence presented to the independent Advisory Committee indicated that eribulin may help some patients live for a little longer, it also caused more undesirable side effects than other treatments already available, and the committee felt that eribulin’s effects on health-related quality of life had not been adequately assessed.”

NICE’s Chief Executive added that the Committee heard from practising clinical experts who told the Institute that patients usually receive sequential treatment with Navelbine (vinorelbine), Xeloda and infrequently Gemzar (gemcitabine).

But Sir Andrew said that experts “stressed” that if Halaven were to be recommended it would “be unlikely” to replace existing treatments “because of its related side-effects”.

Common adverse effects of the treatment include fatigue, alopecia, peripheral, neuropathy, nausea, neutropaenia, leukopaenia and anaemia.

Eisai have again claimed they are “dismayed” at the decision and accused NICE of “not giving enough support to women” and the “physicians who want to treat them”.

Nick Burgin, European Director of Market Access, said: “We hope that NICE grant a rapid re-review as new data is constantly emerging that will help inform their decision.”

Despite the lack of NICE recommendation, Halaven is available through the Government’s Cancer Drugs Fund and is one of the top twelve drugs prescribed through the system.

On the same day as the final NICE guidance, Eisai signed a partnership deal with Valeant Pharmaceuticals to promote and distribute Halaven in eight central and eastern European countries.

NICE has failed to recommend GSK’s Tyverb (lapatinib) or Roche’s Herceptin (trastuzumab) with aromatase inhibitors as first-line treatments for women with breast cancer in a second draft guidance.

Questions were again raised about the cost and effectiveness of both treatments when compared against existing options to delay the growth of advanced breast cancer that has already spread to other parts of the body, and for patients whose tumour cells react with oestrogen or progesterone and have high levels of HER2.

Sir Andrew Dillon, Chief Executive of NICE said that independent analyses indicate that both treatments “do not appear to be cost effective for the NHS” due to “uncertain clinical benefits”.

The second draft guidance follows an appeal from Roche against NICE’s independent Appraisal Committee and its initial findings published in July 2011. The Committee concluded that Herceptin did fulfil the small population criterion within NICE’s “end of life criteria”. This decision was subject to appeal, but upheld by an independent panel in November 2011.

Experts estimate that between 50 and 2,000 postmenopausal women are diagnosed with this type and stage of breast cancer each year. It is believed that the majority of these women are likely to be offered Herceptin as a first-line treatment option.

Tyverb and Herceptin would only usually be considered as first-line options alongside aromatase inhibitors when chemotherapy is deemed unsuitable – but it is unclear how many patients this would be relevant to.

“Having reviewed the available evidence, our committee of experts has found that while both lapatinib and trastuzumab can reduce the growth and further spread of metastatic breast cancer tumours when taken alongside the aromatase inhibitors letrozole and anastrozole, the extent that these treatments can improve overall survival appears to be small or undefined,” said Sir Andrew.

The Scottish Medicines Consortium (SMC) also failed to recommend the use of Tyverb or Herceptin for use on the NHS in Scotland for this particular type and stage of breast cancer when it recently published advice.

NICE’s draft guidance has now been issued for consultation. The deadline for comments to be received is Tuesday 6^th March. The independent Appraisal Committee will then meet to review any submissions.